Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

OBJECTIVE To standardize the strategies for prevention and control of Chikungunya(CHIK)in healthcare in-stitutions so as to reduce the risk of transmission in the institutions.METHODS A working group comprising the ex-perts in hospital infection control,infectious diseases,and microbiology systematically reviewed domestic and international evidence and current guidelines,integrated China's vector ecology and healthcare realities,conducted two rounds of Delphi to achieve expert consensus,and graded the evidence and recommendation strength using the Oxford Centre for Evidence Based Medicine system.RESULTS The consensus issues 18 actionable recommendations on triage,patient mosquito-proof isolation,integrated vector control,protection of susceptible populations,environmental cleaning and disinfection,specimen management,medical textile handling,and outbreak emergency response,with each statement assigned an evi-dence level and recommendation strength.CONCLUSION This consensus is for the first time in China to provide evidence-graded strategies for control of CHIK in healthcare institutions,offering work flow-oriented,implementable guidance for clinicians,laboratorians,and infection-control personnel under different risk scenarios and enhancing the comprehensive coping capacity of the healthcare institutions.

OBJECTIVE To optimize the water extraction technology for Kaixin granules. METHODS UPLC-MS/MS method was established for the simultaneous determination of ginsenoside Rg1， ginsenoside Re， ginsenoside Rb1， tenuifolin， polygalaxanthone Ⅲ and 3， 6′-disinapoyl-sucrose. An orthogonal test was designed with extraction times， extraction duration， and the volume of added water as factors. Using the contents of the aforementioned six indicator components and the extract yield as evaluation indexes， analytic hierarchy process-entropy weight method was employed to determine the combined weights of each indicator. Subsequently， process optimization and validation were conducted by integrating grey relational analysis （GRA） and back propagation （BP） neural network. RESULTS The water extraction technology optimized by the orthogonal test and GRA was 10- fold water for the first decoction and 8-fold water for the subsequent two， extracting 3 times，extracting for 1 h each time； the average comprehensive score of the validation experiment was 91.10 （RSD＝0.31%， n＝3）. The water extraction technology optimized by BP neural network was extracting 3 times with 10-fold water added each time， extracting for 1.5 h each time； the average comprehensive score of the validation experiment was 95.89 （RSD＝0.73%， n＝3）. Considering practical production requirements， the optimal water extraction technology was extraction performed three times， with 10-fold water for the first decoction and 8-fold water for the subsequent two extractions， with an extraction time of 1 h each. CONCLUSIONS The optimized water extraction technology for Kaixin granules is stable and feasible.

Objective:To systematically analyze the registration status of clinical trials related to inflammatory bowel disease (IBD) in China Clinical Trial Registry (ChiCTR); To focus on the characteristics and shortcomings of TCM research; To provide data support and theoretical basis for optimizing clinical trial design and improving the quality of TCM research.Methods:The IBD-related clinical trials registered by ChiCTR from the establishment of the database to September 18, 2024 were retrieved. SPSS 26.0 software was used to analyze the frequency of research objects, registration time, registration area and institution, source of funds, research type and design scheme, random method and blind method, trial staging and research center, sample size, intervention measures and outcome indicators.Results:There were 317 clinical trials of IBD. Shanghai, Jiangsu, Beijing, Guangdong and Zhejiang accounted for 72.87% of the total number of registrations. Most of the registered projects were intervention studies (51.42%), 48 studies used blind method, and randomized controlled study was the main research design type. In the 68 clinical trials related to TCM, the intervention measures were divided into 4 categories, of which Chinese materia medica was the most (42 items); the sample size was the most in the intervention study, with a total of 6 787 cases; the total frequency of outcome indicators was 1 866 times, and the quality of life and mental health were the most (147 items).Conclusions:The number of registered IBD clinical trials is generally increasing, but there may be problems such as uneven distribution of regions and institutions, poor design of sample size, blind method and other research, and non-standard filling of registration information. In the research of TCM treatment of IBD, it is suggested to further strengthen the depth and breadth, especially the characteristic therapy of TCM.

OBJECTIVE To evaluate the quality of Yindan huoxue tongyu granules. METHODS Taking high performance liquid chromatography with ultraviolet and evaporative light scattering detection as method， the fingerprint of 15 batches of Yindan huoxue tongyu granules was established， and similarity evaluation was performed by Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition） to determine common peaks. The common peaks were identified by comparing with reference substance chromatograms and single decoction piece chromatograms. Network pharmacology was used to screen out core targets and pathways of identified components， construct a “component-target-pathway” network diagram， and predict the pharmacodynamic components of Yindan huoxue tongyu granules， and the content determination of these components was carried out by the same method. RESULTS HPLC fingerprints of 15 batches of Yindan huoxue tongyu granules were characterized with 40 common peaks， and 17 components including salvianolic acid B， astragaloside Ⅳ， notoginsenoside R1， and ginkgolide A were identified. Network pharmacology predicted that 17 components mainly acted on 97 core targets and 137 pathways to exert their pharmacological effect. Average contents of 13 bioactive components in 15 batches of samples were 0.126 8， 0.232 0， 0.073 8， 0.353 2， 3.620 2， 0.191 0， 0.333 3， 0.317 4， 0.785 0， 0.538 2， 0.460 0， 2.475 1 and 0.347 7 mg/g， including calycosin-7-O-β-D-glucoside， rosmarinic acid， formononetin， lithospermic acid， salvianolic acid B， ononin， ginsenoside Rb1， ginsenoside Rd， ginkgolide C， ginkgolide A， ginkgolide B， notoginsenoside R1， and astragaloside Ⅳ. CONCLUSIONS The established fingerprint of Yindan huoxue tongyu granules can reflect the overall characteristics of the preparation. The content determination method for its pharmacodynamic components， developed in combination with network pharmacology， is accurate， reliable， and exhibits good repeatability， making it suitable for evaluating the quality of Yindan huoxue tongyu granules.

OBJECTIVE To optimize the forming process of Yindan huoxue tongyu granules， and evaluate the quality of the granules. METHODS Taking forming rate， angle of repose， moisture， moisture absorption rate and dissolution rate as indexes， single factor experiment combined with Plackett-Burman design was adopted to screen key process parameters； analytic hierarchy process combined with entropy weight method and Box-Behnken response surface method were used to optimize the molding process of Yindan huoxue tongyu granules， and the forming process was verified. The relative homogeneity index， bulk density， vibration density， Hausner ratio， angle of repose， moisture and hygroscopicity were used as secondary physical indexes to establish the physical fingerprints of 10 batches of Yindan huoxue tongyu granules to evaluate particle quality consistency. RESULTS The optimal molding process of Yindan huoxue tongyu granules was as follows： mannitol as the fixed excipient， the drug-assisted ratio was 1∶1（m/m） and the drying time was 1 h； 90% ethanol was used as wetting agent and the amount of it was 32%， the drying temperature was 70 ℃. The results of validation tests showed that the average comprehensive score was 97.45， which was close to the predicted value of 97.18. The similarities between the physical fingerprints of 10 batches of Yindan huoxue tongyu granules prepared by the optimal molding process and the reference physical fingerprint were all higher than 0.99. CONCLUSIONS The molding process is stable and feasible， and the quality of Yindan huoxue tongyu granules produced is stable and controllable.

Objective:To study the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with fine needle aspiration biopsy (FNA) for thyroid imaging reporting and data system (TI-RADS) 4 type thyroid micro-nodules (TN).Methods:A total of 121 TI-RADS 4 TN patients admitted to Zhanjiang Central People's Hospital from June 2020 to June 2023 were selected as the research subjects. All patients underwent examinations such as CEUS, FNA, and pathology (as the gold standard). The CEUS manifestations of TI-RADS 4 benign and malignant nodules were observed. The diagnostic accuracy, sensitivity, and specificity of CEUS and FNA alone and in combination for TI-RADS 4 type TN benign and malignant nodules were calculated and compared.Results:Among the 121 patients, there were 109 females and 12 males, with an age of (48.27 ± 7.76) years. Pathological diagnosis showed 74 cases of malignancy and 47 cases of benign. CEUS diagnosed 64 cases of malignancy and 57 cases of benign, with a diagnostic accuracy of 86.49% (64/74); the CEUS manifestations of benign and malignant nodules were compared in terms of enhancement mode, enhancement level, uniformity, peripheral ring shape, and post enhancement boundary, and the differences were statistically significant ( P < 0.001). FNA diagnosed 62 cases of malignancy and 59 cases of benign, with a diagnostic accuracy of 83.78% (62/74). CEUS combined with FNA diagnosed 72 cases of malignancy and 49 cases of benign, with a diagnostic accuracy rate of 97.30% (72/74). The accuracy of CEUS combined with FNA in diagnosing malignant nodules was higher than that of CEUS and FNA alone ( P < 0.05). The sensitivity and specificity of CEUS combined with FNA in diagnosing malignant nodules were higher than those of CEUS and FNA alone ( P < 0.05). Conclusion:The combination of CEUS and FNA has good diagnostic value for TI-RADS 4 type TN, which can improve the accuracy and diagnostic efficiency of malignant nodule diagnosis.

Objective:To study the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with fine needle aspiration biopsy (FNA) for thyroid imaging reporting and data system (TI-RADS) 4 type thyroid micro-nodules (TN).Methods:A total of 121 TI-RADS 4 TN patients admitted to Zhanjiang Central People's Hospital from June 2020 to June 2023 were selected as the research subjects. All patients underwent examinations such as CEUS, FNA, and pathology (as the gold standard). The CEUS manifestations of TI-RADS 4 benign and malignant nodules were observed. The diagnostic accuracy, sensitivity, and specificity of CEUS and FNA alone and in combination for TI-RADS 4 type TN benign and malignant nodules were calculated and compared.Results:Among the 121 patients, there were 109 females and 12 males, with an age of (48.27 ± 7.76) years. Pathological diagnosis showed 74 cases of malignancy and 47 cases of benign. CEUS diagnosed 64 cases of malignancy and 57 cases of benign, with a diagnostic accuracy of 86.49% (64/74); the CEUS manifestations of benign and malignant nodules were compared in terms of enhancement mode, enhancement level, uniformity, peripheral ring shape, and post enhancement boundary, and the differences were statistically significant ( P < 0.001). FNA diagnosed 62 cases of malignancy and 59 cases of benign, with a diagnostic accuracy of 83.78% (62/74). CEUS combined with FNA diagnosed 72 cases of malignancy and 49 cases of benign, with a diagnostic accuracy rate of 97.30% (72/74). The accuracy of CEUS combined with FNA in diagnosing malignant nodules was higher than that of CEUS and FNA alone ( P < 0.05). The sensitivity and specificity of CEUS combined with FNA in diagnosing malignant nodules were higher than those of CEUS and FNA alone ( P < 0.05). Conclusion:The combination of CEUS and FNA has good diagnostic value for TI-RADS 4 type TN, which can improve the accuracy and diagnostic efficiency of malignant nodule diagnosis.

OBJECTIVE To standardize the strategies for prevention and control of Chikungunya(CHIK)in healthcare in-stitutions so as to reduce the risk of transmission in the institutions.METHODS A working group comprising the ex-perts in hospital infection control,infectious diseases,and microbiology systematically reviewed domestic and international evidence and current guidelines,integrated China's vector ecology and healthcare realities,conducted two rounds of Delphi to achieve expert consensus,and graded the evidence and recommendation strength using the Oxford Centre for Evidence Based Medicine system.RESULTS The consensus issues 18 actionable recommendations on triage,patient mosquito-proof isolation,integrated vector control,protection of susceptible populations,environmental cleaning and disinfection,specimen management,medical textile handling,and outbreak emergency response,with each statement assigned an evi-dence level and recommendation strength.CONCLUSION This consensus is for the first time in China to provide evidence-graded strategies for control of CHIK in healthcare institutions,offering work flow-oriented,implementable guidance for clinicians,laboratorians,and infection-control personnel under different risk scenarios and enhancing the comprehensive coping capacity of the healthcare institutions.

Objective:To investigate the effects and mechanisms of glycyrrhetinic acid(GA)on the proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT)of hepatocellular carcinoma SMMC-7721 cells by regulating the β-catenin/transcription factor 4(TCF4)signaling pathway.Methods:HCC cells SMMC-7721 were randomly separated into the control,L-GA,M-GA,H-GA groups(50,100,200 μmol/L GA)and the GA+LiCl group(200 μmol/L GA+40 μmol/L β-catenin activator LiCl).The effects of GA on the proliferation,migration,invasion and apoptosis of SMMC-7721 cells were detected by plate cloning,Transwell experiment and flow cytometry.WB was applied to detect the effects of GA on the expressions of β-catenin/TCF4 signaling pathway proteins(β-catenin、TCF4)and EMT(E-cadherin,vimentin)-related proteins in SMMC-7721 cells.The model of SMMC-7721 cell transplanted tumor in nude mice was established to observe the effects of GA on the growth of transplanted tumor and the expressions of β-catenin and TCF4 proteins.Results:Compared with the control group,SMMC-7721 cell clonal number,migration and invasion numbers,β-catenin,TCF4 and vmentin protein expressions in the L-GA,M-GA and H-GA groups decreased significantly(all P<0.05),while the apoptosis rate and the expression of E-cadherin protein increased(all P<0.05).Compared with the H-GA group,the numbers of clones,migration and invasion,β-catenin,TCF4 and vimentin protein expressions in the GA+LiCl group increased significantly(all P<0.05),while the apoptosis rate and E-cadherin protein expression decreased significantly(all P<0.05).Tumor-bearing nude mouse model experiment showed that the tumor weight and volume and the positive rates of β-catenin and TCF4 proteins in the GA group were significantly lower than those in the control group(all P<0.05).Conclusion:GA can significantly inhibit the proliferation,migration,invasion,and the EMT process of SMMC-7721 cells,thereby inhibiting the progression of HCC.Its mechanism may be achieved by inhibiting the β-catenin/TCF4 signaling pathway.